Cuvelier, Geraldine and Vermonden, Perrine and Debisschop, Pauline and Martin, Manon and Derouane, Francoise and Liebisch, Gerhard and Ecker, Josef and Hoering, Marcus and Berliere, Martine and Van Bockstal, Mieke and Galant, Christine and Duhoux, Francois and Mourao, Larissa and Scheele, Colinda and Feron, Olivier and Rezsohazy, Rene and Corbet, Cyril and Larondelle, Yvan (2025) Jacaric Acid Empowers RSL3-Induced Ferroptotic Cell Death in Two- and Three-Dimensional Breast Cancer Cell Models. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (7): 3375. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Ferroptosis has recently emerged as a promising strategy to combat therapy-resistant cancers. As lipid peroxidation is a key trigger of ferroptotic cell death, enhancing cancer cell susceptibility through the supply of highly peroxidisable fatty acids represents a novel therapeutic approach. Conjugated linolenic acids (CLnAs) fulfill this requirement, exhibiting a peroxidation propagation rate eight times higher than their non-conjugated counterpart, alpha-linolenic acid. This study evaluates jacaric acid (JA), a plant-derived CLnA, as a ferroptotic inducer, both as a monotherapy and in combination with RAS-selective lethal 3 (RSL3), a canonical ferroptosis inducer, in 2D and 3D breast cancer cell models. JA treatment significantly reduced cell viability across all models, primarily through lipid peroxidation driven by JA incorporation into cellular lipids rather than alterations in anti-ferroptotic gene expression. Moreover, JA synergistically enhanced RSL3 cytotoxicity under 2D and several 3D conditions. Similar effects were observed with punicic acid, another plant-derived CLnA isomer. Our study exploits a common feature of cancer metabolism, increased fatty acid uptake, to turn it into a vulnerability. The incorporation of JA into breast cancer cells creates a highly peroxidisable environment that increases cancer cell sensitivity to RSL3, potentially reducing required doses and minimising side effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONJUGATED LINOLENIC ACIDS; IN-VITRO; PEROXIDATION; MECHANISMS; ferroptosis; jacaric acid; conjugated linolenic acids; breast organoids; lipid peroxidation; cancer |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2026 05:19 |
| Last Modified: | 31 Mar 2026 05:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67901 |
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